Studies on the Phthalidation of Heteroarenes: A Facile Preparation of 3-(Heteroaryl)phthalides via Triflic Acid Mediated Phthalidation

Meganathan Nandakumar; Elumalai Sankar; Arasambattu K. Mohanakrishnan

doi:10.1055/s-0033-1340551

Synlett, Table of Contents

Synlett 2014; 25(4): 509-514
DOI: 10.1055/s-0033-1340551

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Studies on the Phthalidation of Heteroarenes: A Facile Preparation of 3-(Heteroaryl)phthalides via Triflic Acid Mediated Phthalidation

Meganathan Nandakumar

Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India Fax: +91(44)22352494 Email: mohanakrishnan@unom.ac.in Email: mohan_67@hotmail.com

,

Elumalai Sankar

Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India Fax: +91(44)22352494 Email: mohanakrishnan@unom.ac.in Email: mohan_67@hotmail.com

,

Arasambattu K. Mohanakrishnan*

Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India Fax: +91(44)22352494 Email: mohanakrishnan@unom.ac.in Email: mohan_67@hotmail.com

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Abstract

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Abstract

A triflic acid mediated heteroarylation of phthalaldehydic acid in 1,2-dichloroethane at reflux temperature leads to the formation of 3-heteroarylphthalides. This method for the phthalidation of heteroarenes can be utilized for the successful preparation of mono-, bis- and tris-heteroarylphthalides.

Key words

triflic acid - heteroarylation - 3-heteroarylphthalides - Brønsted acid - Lewis acid

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References

References and Notes

1a Senthil Kumar N, Arul Clement J, Mohanakrishnan AK. Tetrahedron 2009; 65: 822
1b Arul Clement J, Gunasekaran P, Mohanakrishnan AK. Tetrahedron 2009; 65: 4113
1c Senthil Kumar N, Mohanakrishnan AK. Tetrahedron 2010; 66: 5660
1d Nandakumar M, Sivasakthikumaran R, Mohanakrishnan AK. Eur. J. Org. Chem. 2012; 3647

2 Kato S, Nonoyama N, Tomimoto K, Mase T. Tetrahedron Lett. 2002; 43: 7315

3a Kondo Y, Asai M, Miura T, Uchiyama M, Sakamoto T. Org. Lett. 2001; 3: 13
3b Jensen AE, Dohle W, Sapountzis I, Lindsay DM, Au VA, Knochel P. Synthesis 2002; 565
3c Nagaki A, Kim H, Yoshida J.-I. Angew. Chem. 2008; 47: 7833
3d Nagaki A, Kim H, Moriwaki Y, Matsuo C, Yoshida J.-I. Chem. Eur. J. 2010; 16: 11167

4 Rayabarapu D, Chang HT, Cheng C.-H. Chem. Eur. J. 2004; 10: 2991

5a Ye Z, Lv G, Wang W, Zhang M, Cheng J. Angew. Chem. Int. Ed. 2010; 49: 3671
5b Ye Z, Qian P, Lv G, Luo F, Cheng J. J. Org. Chem. 2010; 75: 6043
5c Karthikeyan J, Parthasarathy K, Cheng C.-H. Chem Commun. 2011; 47: 10461

6a Al-Hamdany R, Al-Rawi J.-M. J. Prakt. Chem. 1987; 329: 126
6b Al-Hamdany R, Fataftah ZA. Asian J. Chem. 1997; 9: 703

7 Meek ST, Nesterov EE, Swager TM. Org. Lett. 2008; 10: 2991
8 Newman MS, Venkateswaran S, Sankaran V. J. Org. Chem. 1975; 40: 2996

9a Canonne P, Plamondon J, Akssira M. Tetrahedron 1988; 44: 2903
9b Knepper K, Ziegert RE, Bräse S. Tetrahedron 2004; 60: 8591
9c Itoh T, Matsuno M, Kamiya E, Hirai K, Tomioka H. J. Am. Chem. Soc. 2005; 127: 7078

10 Kuriyama M, Ishiyama N, Shimazawa R, Shirai R, Onomura O. J. Org. Chem. 2009; 74: 9210
11 Lin H, Sun X.-W. Tetrahedron Lett. 2008; 49: 5343
12 Mohanakrishnan AK, Huckey A, Lyon MA, Lakshmikantham MV, Cava MP. Tetrahedron 1999; 55: 11745

13a Sivasakthikumaran R, Nandakumar M, Mohanakrishnan AK. J. Org. Chem. 2012; 77: 9053
13b Sureshbabu R, Saravanan V, Dhayalan V, Mohanakrishnan AK. Eur. J. Org. Chem. 2011; 922
13c Dhayalan V, Arul Clement J, Jagan R, Mohanakrishnan AK. Eur. J. Org. Chem. 2009; 531

14 General Procedure: Phthalidation of N-Hexylcarbazole (2a): To a stirred suspension of N-hexylcarbazole 2a (0.30 g, 1.20 mmol), 2-carboxybenzaldehyde (0.22 g, 1.43 mmol) and anhyd MgSO4 (0.29 g, 1.20 mmol) in anhyd DCE (15 mL), 3 drops of triflic acid (0.04 g, 0.024 mmol) were added, and the mixture was refluxed for 3 h. It was then poured into sat. NaHCO3 solution (50 mL), and the resulting mixture was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with H2O (2 × 30 mL) and dried (Na2SO4). Removal of the solvent followed by column chromatographic purification (silica gel, 10% EtOAc in hexane) afforded lactone 3a as a thick pale-yellow liquid (0.37 g, 80% yield). 1H NMR (300 MHz, CDCl3): δ = 8.06–8.00 (m, 3 H, ArH), 7.64–7.55 (m, 2 H, ArH), 7.52–7.47 (m, 1 H, ArH), 7.42–7.32 (m, 3 H, ArH), 7.29–7.22 (m, 2 H, ArH), 6.58 (s, 1 H, CH), 4.24 (t, J = 7.2 Hz, 2 H, CH2), 1.87–1.78 (m, 2 H, CH2), 1.34–1.27 (m, 6 H, CH2), 0.90–0.86 (m, 3 H, CH3). 13C NMR (75 MHz, CDCl3): δ = 170.7, 150.2, 140.7, 134.1, 129.0, 126.2, 126.0, 125.8, 125.3, 124.7, 123.0, 122.8, 122.3, 120.3, 119.6, 119.0, 109.0, 108.8, 83.8, 43.0, 31.4, 28.7, 26.7, 22.4, 13.9. ��

For syntheses of benzo[c]thiophenes, see ref. 7 and:

15a Kiebooms RH. L, Adriaensens PJ. A, Vanderzande DJ. N, Gelan JM. J. V. J. Org. Chem. 1997; 62: 1473
15b Mohanakrishnan AK, Lakshmikantham MV, McDougal CD, Cava MP, Baldwin JW, Metzger RM. J. Org. Chem. 1998; 63: 3105
15c Kisselev R, Thelakkat M. Macromolecules 1998; 37: 8951
15d Raimundo JM, Blanchard P, Brisset H, Akoudad S, Roncali J. Chem. Commun. 2000; 939
15e Hansel H, Zettl H, Krausch G, Kisselev R, Thelakkat M, Schmidt HW. Adv. Mater. 2003; 15: 2056
15f Amaladass P, Arul Clement J, Mohanakrishnan AK. Eur. J. Org. Chem. 2008; 3798

For applications of benzo[c]thiophenes, see:

16a Strassler C, Davis NE, Kool ET. Helv. Chim. Acta 1999; 82: 2160
16a Silva TJ. L, Mendes PJ, Garcia MH, Robalo MP, Ramalho JP. P, Cavalho AJ. P, Buchert M, Wittenburg C, Heck J. Eur. J. Inorg. Chem. 2013; 3506
16c Nesterov EE, Skoch J, Hyman B, Klunk WE, Bacskai BJ, Swager TM. Angew. Chem. Int. Ed. 2005; 44: 5452

17a Bouas-Laurent H, Castellan A, Desvergne J.-P, Lapouyade R. Chem. Soc. Rev. 2000; 29: 43
17b Okamoto K, Kawamura T, Sone M, Ogino K. Liquid Crystals 2007; 34: 1001
17c Mamada M, Minamiki T, Katagiri H, Tokito S. Org. Lett. 2012; 14: 4062
17d Chen Y.-H, Lin S.-L, Chang Y.-C, Chen Y.-C, Lin J.-T, Lee R.-H, Kuo WJ, Jeng RJ. Org. Electron. 2012; 13: 43
17e Nakano M, Niimi K, Miyazaki E, Osaka I, Takimiya K. J. Org. Chem. 2012; 77: 8099

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